三环哌酯对海马脑片神经元烟碱受体及谷氨酸能兴奋性突触传递的阻断作用  

Blockade effects of tricyclopinate on nicotinic acetylcholine receptor and synaptic transmission in hippocampal slices

作　　者：胡琦[1] 刘振伟[1] 刘传缋[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国药理学与毒理学杂志》2007年第5期393-398,共6页Chinese Journal of Pharmacology and Toxicology

摘　　要：目的研究中枢抗胆碱药三环哌酯(TCPN)对海马脑片神经元烟碱受体(nAChR)及谷氨酸能兴奋性突触传递的阻断作用。方法采用海马脑片盲法全细胞记录技术,以自发兴奋性与抑制性突触后电流(sEPSC和sIPSC)为观测指标。结果TCPN(10～500μmol.L-1)浓度依赖地对抗nAChR激动剂碘化二甲基苯基哌嗪(DMPP)增强海马脑片CA1锥体神经元sEPSC的作用,500μmol.L-1完全阻断DMPP的增强作用。同时,TCPN浓度依赖地直接抑制神经元的sEPSC。但TCPN不抑制神经元的sIPSC,也不阻断DMPP对sIPSC的增强作用。结论TCPN对海马脑片神经元突触传递的影响具有双重作用,既能通过阻断谷氨酸能突触前末梢nAChR而抑制sEPSC,同时还能直接抑制sEPSC。AIM To study the effects of tricyclopinate （TCPN）, an anti-cholinergic drug in central nervous system, on nicotinic acetylcholine receptor （nAChR） and synaptic activity of CA1 pyramidal neuron in hippocampal slices. METHODS Blind whole-cell recording in neurons of CA1 area in rat hippocampal slice was performed to record spontaneous excitatory and inhibitory postsynaptic currents （sEPSC and slPSC ）. RESULTS Dimethylphenylpiperazinium iodide （DMPP, an agonist of nAChR） significantly increased the sEPSC and slPSC frequency in CA1 pyramidal neuron, and TCPN concentration-dependently suppressed this enhancement of sEPSC, but not slPSC. TCPN 100 μmol·L^-1 suppressed this sEPSC enhancement, while 500 μmol·L^-1 TCPN could block it completely. Meanwhile, TCPN also showed directly inhibitory effect on sEPSC of CA1 pyramidal neuron. TCPN 500μmol·L^-1 completely blocked all sEPSC. CONCLUSION TCPN, as an anti-cholinergic drug in central nervous system, has both the inhibitory effect on excitatory transmission and the blockade effect on presynaptic nAChR in CA1 neurons of hippocampal slices.

关 键 词：三环哌酯 受体 烟碱 海马 膜片钳技术 全细胞 突触后电流 

分 类 号：R96[医药卫生—药理学]